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Longitudinal Circulating Tumor DNA Analysis in Blood and Saliva for Prediction of Response to Osimertinib and Disease Progression in EGFR-Mutant Lung Adenocarcinoma

SIMPLE SUMMARY: ctDNA assay is a promising non-invasive method to detect genomic alterations associated with lung cancer. In this prospective study of 25 patients with EGFR-mutant lung adenocarcinoma receiving osimertinib, ctDNA progression predated radiographic progression by 118 days in 11 of 20 p...

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Autores principales: Kim, Chul, Xi, Liqiang, Cultraro, Constance M., Wei, Fang, Jones, Gregory, Cheng, Jordan, Shafiei, Ahmad, Pham, Trinh Hoc-Tran, Roper, Nitin, Akoth, Elizabeth, Ghafoor, Azam, Misra, Vikram, Monkash, Nina, Strom, Charles, Tu, Michael, Liao, Wei, Chia, David, Morris, Clive, Steinberg, Seth M., Bagheri, Hadi, Wong, David T. W., Raffeld, Mark, Guha, Udayan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268167/
https://www.ncbi.nlm.nih.gov/pubmed/34283064
http://dx.doi.org/10.3390/cancers13133342
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author Kim, Chul
Xi, Liqiang
Cultraro, Constance M.
Wei, Fang
Jones, Gregory
Cheng, Jordan
Shafiei, Ahmad
Pham, Trinh Hoc-Tran
Roper, Nitin
Akoth, Elizabeth
Ghafoor, Azam
Misra, Vikram
Monkash, Nina
Strom, Charles
Tu, Michael
Liao, Wei
Chia, David
Morris, Clive
Steinberg, Seth M.
Bagheri, Hadi
Wong, David T. W.
Raffeld, Mark
Guha, Udayan
author_facet Kim, Chul
Xi, Liqiang
Cultraro, Constance M.
Wei, Fang
Jones, Gregory
Cheng, Jordan
Shafiei, Ahmad
Pham, Trinh Hoc-Tran
Roper, Nitin
Akoth, Elizabeth
Ghafoor, Azam
Misra, Vikram
Monkash, Nina
Strom, Charles
Tu, Michael
Liao, Wei
Chia, David
Morris, Clive
Steinberg, Seth M.
Bagheri, Hadi
Wong, David T. W.
Raffeld, Mark
Guha, Udayan
author_sort Kim, Chul
collection PubMed
description SIMPLE SUMMARY: ctDNA assay is a promising non-invasive method to detect genomic alterations associated with lung cancer. In this prospective study of 25 patients with EGFR-mutant lung adenocarcinoma receiving osimertinib, ctDNA progression predated radiographic progression by 118 days in 11 of 20 patients with disease progression. Saliva-based ctDNA analysis and plasma NGS detected additional patients with ctDNA progression preceding clinical progression, suggesting the potential complementary roles of different ctDNA detection methodologies. Baseline mutant ctDNA level predicted progression-free survival while tumor volume measurements by volumetric CT did not. Serial ctDNA analysis of plasma and saliva is a clinically useful tool to monitor response and resistance to osimertinib. ABSTRACT: Background: We assessed whether serial ctDNA monitoring of plasma and saliva predicts response and resistance to osimertinib in EGFR-mutant lung adenocarcinoma. Three ctDNA technologies—blood-based droplet-digital PCR (ddPCR), next-generation sequencing (NGS), and saliva-based EFIRM liquid biopsy (eLB)—were employed to investigate their complementary roles. Methods: Plasma and saliva samples were collected from patients enrolled in a prospective clinical trial of osimertinib and local ablative therapy upon progression (NCT02759835). Plasma was analyzed by ddPCR and NGS. Saliva was analyzed by eLB. Results: A total of 25 patients were included. We analyzed 534 samples by ddPCR (n = 25), 256 samples by NGS (n = 24) and 371 samples by eLB (n = 22). Among 20 patients who progressed, ctDNA progression predated RECIST 1.1 progression by a median of 118 days (range: 61–272 days) in 11 (55%) patients. Of nine patients without ctDNA progression by ddPCR, two patients had an increase in mutant EGFR by eLB and two patients were found to have ctDNA progression by NGS. Levels of ctDNA measured by ddPCR and NGS at early time points, but not volumetric tumor burden, were associated with PFS. EGFR/ERBB2/MET/KRAS amplifications, EGFR C797S, PIK3CA E545K, PTEN V9del, and CTNNB1 S45P were key resistance mechanisms identified by NGS. Conclusion: Serial assessment of ctDNA in plasma and saliva predicts response and resistance to osimertinib, with each assay having supplementary roles.
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spelling pubmed-82681672021-07-10 Longitudinal Circulating Tumor DNA Analysis in Blood and Saliva for Prediction of Response to Osimertinib and Disease Progression in EGFR-Mutant Lung Adenocarcinoma Kim, Chul Xi, Liqiang Cultraro, Constance M. Wei, Fang Jones, Gregory Cheng, Jordan Shafiei, Ahmad Pham, Trinh Hoc-Tran Roper, Nitin Akoth, Elizabeth Ghafoor, Azam Misra, Vikram Monkash, Nina Strom, Charles Tu, Michael Liao, Wei Chia, David Morris, Clive Steinberg, Seth M. Bagheri, Hadi Wong, David T. W. Raffeld, Mark Guha, Udayan Cancers (Basel) Article SIMPLE SUMMARY: ctDNA assay is a promising non-invasive method to detect genomic alterations associated with lung cancer. In this prospective study of 25 patients with EGFR-mutant lung adenocarcinoma receiving osimertinib, ctDNA progression predated radiographic progression by 118 days in 11 of 20 patients with disease progression. Saliva-based ctDNA analysis and plasma NGS detected additional patients with ctDNA progression preceding clinical progression, suggesting the potential complementary roles of different ctDNA detection methodologies. Baseline mutant ctDNA level predicted progression-free survival while tumor volume measurements by volumetric CT did not. Serial ctDNA analysis of plasma and saliva is a clinically useful tool to monitor response and resistance to osimertinib. ABSTRACT: Background: We assessed whether serial ctDNA monitoring of plasma and saliva predicts response and resistance to osimertinib in EGFR-mutant lung adenocarcinoma. Three ctDNA technologies—blood-based droplet-digital PCR (ddPCR), next-generation sequencing (NGS), and saliva-based EFIRM liquid biopsy (eLB)—were employed to investigate their complementary roles. Methods: Plasma and saliva samples were collected from patients enrolled in a prospective clinical trial of osimertinib and local ablative therapy upon progression (NCT02759835). Plasma was analyzed by ddPCR and NGS. Saliva was analyzed by eLB. Results: A total of 25 patients were included. We analyzed 534 samples by ddPCR (n = 25), 256 samples by NGS (n = 24) and 371 samples by eLB (n = 22). Among 20 patients who progressed, ctDNA progression predated RECIST 1.1 progression by a median of 118 days (range: 61–272 days) in 11 (55%) patients. Of nine patients without ctDNA progression by ddPCR, two patients had an increase in mutant EGFR by eLB and two patients were found to have ctDNA progression by NGS. Levels of ctDNA measured by ddPCR and NGS at early time points, but not volumetric tumor burden, were associated with PFS. EGFR/ERBB2/MET/KRAS amplifications, EGFR C797S, PIK3CA E545K, PTEN V9del, and CTNNB1 S45P were key resistance mechanisms identified by NGS. Conclusion: Serial assessment of ctDNA in plasma and saliva predicts response and resistance to osimertinib, with each assay having supplementary roles. MDPI 2021-07-03 /pmc/articles/PMC8268167/ /pubmed/34283064 http://dx.doi.org/10.3390/cancers13133342 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Chul
Xi, Liqiang
Cultraro, Constance M.
Wei, Fang
Jones, Gregory
Cheng, Jordan
Shafiei, Ahmad
Pham, Trinh Hoc-Tran
Roper, Nitin
Akoth, Elizabeth
Ghafoor, Azam
Misra, Vikram
Monkash, Nina
Strom, Charles
Tu, Michael
Liao, Wei
Chia, David
Morris, Clive
Steinberg, Seth M.
Bagheri, Hadi
Wong, David T. W.
Raffeld, Mark
Guha, Udayan
Longitudinal Circulating Tumor DNA Analysis in Blood and Saliva for Prediction of Response to Osimertinib and Disease Progression in EGFR-Mutant Lung Adenocarcinoma
title Longitudinal Circulating Tumor DNA Analysis in Blood and Saliva for Prediction of Response to Osimertinib and Disease Progression in EGFR-Mutant Lung Adenocarcinoma
title_full Longitudinal Circulating Tumor DNA Analysis in Blood and Saliva for Prediction of Response to Osimertinib and Disease Progression in EGFR-Mutant Lung Adenocarcinoma
title_fullStr Longitudinal Circulating Tumor DNA Analysis in Blood and Saliva for Prediction of Response to Osimertinib and Disease Progression in EGFR-Mutant Lung Adenocarcinoma
title_full_unstemmed Longitudinal Circulating Tumor DNA Analysis in Blood and Saliva for Prediction of Response to Osimertinib and Disease Progression in EGFR-Mutant Lung Adenocarcinoma
title_short Longitudinal Circulating Tumor DNA Analysis in Blood and Saliva for Prediction of Response to Osimertinib and Disease Progression in EGFR-Mutant Lung Adenocarcinoma
title_sort longitudinal circulating tumor dna analysis in blood and saliva for prediction of response to osimertinib and disease progression in egfr-mutant lung adenocarcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268167/
https://www.ncbi.nlm.nih.gov/pubmed/34283064
http://dx.doi.org/10.3390/cancers13133342
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